Abstract IA23: Molecular landscapes of hepatocellular carcinoma and cholangiocarcinoma

Abstract

Abstract Liver cancer is among the top five deadliest cancers in the world, especially in Southeast Asia and Sub-Saharan Africa, and its incidence rates continue to increase in recent decades. Despite considerable efforts towards the development of new prevention, diagnosis and treatment strategies, the improvement of cancer survival is modest. Defined as the unique genotypic and phenotypic differences of cancer cells within a single tumor (intra-tumor) or amongst different patients (inter-tumor), tumor heterogeneity has consistently been linked to worse clinical outcomes in liver cancer. Primary liver cancer mainly consists of two clinical types, i.e., hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), each of which could be further divided into several clinical and molecular subtypes. Chronic liver diseases due to viral hepatitis, alcohol consumption, chemical carcinogens, or nonalcoholic fatty liver disease/nonalcoholic steatohepatitis, are major global health burdens that increase the risk of HCC while parasitic infections may be linked to CCA. It is unclear how complex etiological factors determine tumor subtypes and whether common features may be shared among HCC and CCA. Given the presence of so many clinical and molecular variables, it is imperative to develop well-defined cohorts that include diverse etiologies, race/ethnicities, sex and age, which provides an unbiased platform by minimizing confounding factors to study liver cancer types. Accordingly, we have established several national and international collaborative projects, including the NCI-CLARITY study, the NCI-UMD cohort study, the NCI-Mongolian cohort study, and the TIGER-LC (Thailand) consortium. We have applied molecular-based technologies such as genomics, transcriptomics, metabolomics and microbiomics, including single-cell omics to comprehensively analyze biopsies from diverse populations, in order to better characterize heterogeneity among and within patients, to further define tumor molecular subtypes with unique tumor biology and to understand tumor evolution in response to treatment. These studies have led to the discovery of new cell types and drivers in HCC and CCA, potential new mechanisms of therapy resistance and tumor progression, and new insights into the evolutionary patterns of liver cancer. Our past and future ability to translate our research findings towards patient management through the identification of molecular-based knowledge for understanding of liver cancer pathophysiology with the application of early detection and treatment of liver cancer may have a considerable impact on clinical practice and public health. Citation Format: Xin Wei Wang. Molecular landscapes of hepatocellular carcinoma and cholangiocarcinoma [abstract]. In: Proceedings of the AACR Special Conference: Advances in the Pathogenesis and Molecular Therapies of Liver Cancer; 2022 May 5-8; Boston, MA. Philadelphia (PA): AACR; Clin Cancer Res 2022;28(17_Suppl):Abstract nr IA23.